Divergent functions through alternative splicing: The Drosophila CRMP gene in pyrimidine metabolism, brain, and behavior

Morris, D. H., Dubnau, J., Park, J. H., Rawls Jr, J. M. (August 2012) Divergent functions through alternative splicing: The Drosophila CRMP gene in pyrimidine metabolism, brain, and behavior. Genetics, 191 (4). pp. 1227-1238. ISSN 0016-6731

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URL: http://www.ncbi.nlm.nih.gov/pubmed/22649077
DOI: 10.1534/genetics.112.141101

Abstract

DHP and CRMP proteins comprise a family of structurally similar proteins that perform divergent functions, DHP in pyrimidine catabolism in most organisms and CRMP in neuronal dynamics in animals. In vertebrates, one DHP and five CRMP proteins are products of six genes; however, Drosophila melanogaster has a single CRMP gene that encodes one DHP and one CRMP protein through tissue-specific, alternative splicing of a pair of paralogous exons. The proteins derived from the fly gene are identical over 90% of their lengths, suggesting that unique, novel functions of these proteins derive from the segment corresponding to the paralogous exons. Functional homologies of the Drosophila and mammalian CRMP proteins are revealed by several types of evidence. Loss-of-function CRMP mutation modifies both Ras and Rac misexpression phenotypes during fly eye development in a manner that is consistent with the roles of CRMP in Ras and Rac signaling pathways in mammalian neurons. In both mice and flies, CRMP mutation impairs learning and memory. CRMP mutant flies are defective in circadian activity rhythm. Thus, DHP and CRMP proteins are derived by different processes in flies (tissue-specific, alternative splicing of paralogous exons of a single gene) and vertebrates (tissue-specific expression of different genes), indicating that diverse genetic mechanisms have mediated the evolution of this protein family in animals.

Item Type: Paper
Subjects: organism description > animal > insect > Drosophila
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
organism description > animal behavior
organs, tissues, organelles, cell types and functions > organs types and functions > brain
organism description > animal > insect
organs, tissues, organelles, cell types and functions > organs types and functions > metabolism
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > splicing factor
CSHL Authors:
Communities: CSHL labs > Dubnau lab
Depositing User: Matt Covey
Date: August 2012
Date Deposited: 30 Jan 2013 16:15
Last Modified: 09 Apr 2013 14:53
PMCID: PMC3416003
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27006

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